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Title: A new metal binding domain involved in cadmium, cobalt and zinc transport

The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, but bioinformatics analyses indicate that a diversity of MBDs may exist in nature. In this paper, we report the biochemical, structural and functional characterization of a new MBD from the Cupriavidus metallidurans P1B-4-ATPase CzcP (CzcP MBD). The CzcP MBD binds two Cd2+, Co2+ or Zn2+ ions in distinct and unique sites and adopts an unexpected fold consisting of two fused ferredoxin-like domains. Both in vitro and in vivo activity assays using full-length CzcP, truncated CzcP and several variants indicate a regulatory role for the MBD and distinct functions for the two metal binding sites. Finally, taken together, these findings elucidate a previously unknown MBD and suggest new regulatory mechanisms for metal transport by P1B-ATPases.
 [1] ;  [2] ;  [2] ;  [1]
  1. Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences. Dept. of Chemistry
  2. Wayne State Univ., Detroit, MI (United States). School of Medicine. Dept. of Pharmaceutical Sciences. Cardiovascular Research Inst.
Publication Date:
OSTI Identifier:
Grant/Contract Number:
AC02-98CH10886; GM58518; DK068139; F32GM105339; T32HL120822
Accepted Manuscript
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 11; Journal Issue: 9; Journal ID: ISSN 1552-4450
Nature Publishing Group
Research Org:
Northwestern Univ., Evanston, IL (United States)
Sponsoring Org:
USDOE; National Inst. of Health (NIH) (United States)
Contributing Orgs:
Wayne State Univ., Detroit, MI (United States)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Bioinorganic chemistry; Metals; Transporters; X-ray crystallography